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Increasing general autophagy as a treatment for neurodegenerative diseases like Parkinson’s Disease

[Rhonda]: In the case of mitophagy here, it’s
also it plays an important role in the prevention of neurodegenerative diseases. Correct? [Dr. Kroemer]: Yes. So, most known neurodegenerative diseases
are either caused by the aggregation of poorly built protein cell that somehow create protein
aggregates that are toxic for the cell. Or they can also be caused by septal deficiencies
in the autophagic and lysosomal machineries that lead to the accumulation of unfolded
proteins at the end. And so, either the excessive production of
unfolded proteins or their reduced removal causes to a slow accumulation of these toxic
protein aggregates. Remember that neurodegenerative diseases are
slow processes in most cases that manifests with old age. And so, one strategy to treat neurodegeneration,
at least theoretically, is to increase autophagic turnover. And so, one technique is actually then to
stimulate general autophagy by increasing the demand, by starvation, or by biochemical
trickster that substitute for starvation, and to reduce the protein aggregates that
are the cause of the disease. [Rhonda]: So these protein aggregates like
amyloid beta plaques in Alzheimer’s disease or alpha-synuclein in Parkinson’s disease. So, basically, the clearing out of those protein
aggregates obviously would play an important role not only in prevention but presumably
also, to some degree, in help with the treatment. Of course, that’s you know, an speculation,
but… And then the mitochondria, the one I was thinking
about with mitophagy, was the role, at least some of the proteins that are involved in
that, like, the PINK/Parkin, and how they seem to be important for Parkinson’s disease. Is that accurate? [Dr. Kroemer]: Yeah. So the PINK/Parkin pathway is one pathway
among others, that allows for marking mitochondria that are damaged for destruction. And so, inhibition of this pathway leads to
the accumulation of malfunctioning mitochondria with major consequences for the cell that
harbours cells’ mitochondria because all of a sudden bioenergetic metabolism becomes inefficient,
reactive oxygen species are produced, and as you know, mitochondria are latent bombs
in the sense that they enclose potentially dangerous proteins that once released will
activate the apoptotic machinery and cause cellular suicide. [Rhonda]: Yeah.

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